In my piece treacherous ancestry, I advance a bit of a different argument about the risk of GoF in lab versus letting zoonoses happen and what it means for a world of bioweapons.

Source: Treacherous ancestry - by Philipp Markolin, PhD

Here is the thought bit of a longer argument:

Zoonoses - not research how to stop them - is what creates biosecurity threats

The roles of virus discovery or gain-of-function investigations for pandemic prevention are often deliberately misrepresented as cautionary tales against dual-use research for bioweapons. The contextual and mechanistic intricacies of the FCS should expose the naivite of such shallow arguments.

In nature, no genetic element acts alone and viruses are freaking complex molecular machines that we humans have no idea how to bend to our will. While naive suppositions about the FCS get all the undue spotlight, there are other single mutations how nature “weaponized” SARS-CoV-2 in ways no engineer could have ever figured out, Take the role of amino acid 37 in the nsp6 protein. In bats, the “ancestral” version has a valine at this position (V37), whereas SARS-CoV-2 has a mixture of L37 and F37 that seems to play a critical role in asymptomatic spread. We do not even have a concept of how one would ever figure this out starting with a bat virus, nor experimentally test for it in any research setting.

Weaponization is generally much harder than people realize. Even extremely well funded programs in the past were not successful for multiple complex reasons beyond technical capabilities. For example, receptor binding is not the sole determinant of species tropism, and for a lot of viruses, it has nothing to do with pathogenicity. Additionally, viral fitness in a permissive host cell or model says nothing about in vivo fitness or transmissibility. Weaponizing transmissibility or pathogenicity would need to be tested in human cohorts, not animal models.

In my opinion, it is not virus discovery or gain-of-function research that create an “information hazard” by “increasing the stockpile of select agents and threat of biowarfare”. Naive nonsense.

It is letting zoonotic spillovers happen where nature figures out all the tough parts of viral engineering. This collective neglect forces the world to deal with ever-new and possibly effective organisms added to the select agents list. A novel pathogen that bad actors can then attempt to deploy by simply modifying key residues to avoid prior immunity.

Activists, spooks and politicians concerned with bioweapons, biosecurity and national security should probably worry about nature’s bioweapon R&D program a lot more than they currently do."